In my kid’s case, it appears that 2 exons , 45 and 51 need to get skipped ( His molecular diagnostic report says ‘ Out of frame deletion of exon 46 to 50’).
I just wanted to understand if there are any work going on which can help in skipping 2 exons (45 and 51). Whether even this is possible also or no.

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Thanks John. Your points are very valid.
I also do NOT have answers for these at the moment.I guess, we all need to discuss these with relevant folks to get the answers.

I emailed Dr. Aartsma-Rus about this just the other day, since our son, Liam, also has the deletion of exons 46-50. Here is her reply:

Liam's mutation is relatively common and indeed would need double exon skipping to restore the genetic code. Double exon skipping is possible in cultured cells. However, translating it into the human situation is far more complex than for single exon skipping. The reason for this is the fact that both exons need to be skipped. In cultured cells it is possible to just add compounds for exon 45 skipping and exon 51 skipping at very high doses. However, in living organisms one is limited because of toxicity and feasibility. The doses currently used in humans for single exon skipping are probably at the top of what is safe (for one of the chemistries) and what is feasible (for the other chemistry - this is has to do with solubility of the compounds). These doses only lead to minor levels of skipping a single exon. When two exons need to be skipped, most likely a higher dose of each individual exon skipping compound is needed (because you need to target both exons in the same transcript, e.g. if 10% of the transcript are targeted by each exon skipping compound, only 1% of the transcripts are targeted by both compounds, so you get a dilution of the effect - since you would be dosing at half the optimal dose, it might even be worse...).

Hopefully additonal studies in animals will be done to sort this out in the future. Multiple things are possible, e.g. having more efficient exon skipping compounds, or finding a way of dosing that is optimal for double exon skipping, but still feasible and tolerable. However, this would require a lot more work, so in the near future in all likelihood double exon skipping will not be done for humans.

I am sorry to be the bearer of this dissapointing news. Please note that there are other therapeutic approaches in development that would apply to all patients regardless of their mutation. Hopefully one or more of these will work out. Also note that the exon skipping field is still working on double exon skipping - we just have come to the realisation that it is a lot more trickier than we initially thought.

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